The invention relates to a method and apparatus for mass spectrometric analysis of gases and liquids and constituents thereof such as may be received from a gas or liquid chromatograph.
Major limitations exist in current mass spectrometric ionization techniques in the methods used to volatilize the analytes. Electron impact, photoionization, ion-molecule charge transfer, and thermal ionization are a number of methods by which the ionization can be accomplished. However, heat is used almost universally to effect volatilization. Many large molecules and biologically important compounds can not be determined using mass spectrometry due to their thermally sensitive nature. Heat induced decomposition and fragmentation of these unstable compounds occurs prior to detection by the mass analyzer.
Electron impact, chemical ionization, thermospray, and direct liquid introduction require the input of thermal energy to accomplish or maintain the volatility of the analyte. Atmospheric pressure ionization also uses heat to assist in the volatilization of liquid samples. The plasma desorption techniques, laser desorption, fast atom bombardment, and californium-252 desorption are at least partially dependent on thermal energy to accomplish volatilization and ionization of the analyte. Both fast atom bombardment and californium-252 are further restricted because no method currently exists to interface them directly with any chromatographic separation techniques. Ion evaporation, a non-thermal ion separation method, and thermospray require either that the analytes exist in ionized form in aqueous solvent or that the analytes can be protonated through ion-molecule proton transfer reactions from an aqueous buffered solvent for detection by the mass analyzer. Gases and compounds which are insoluble or uncharged in aqueous solvents are not analyzed by these methods. This restriction limits the application of these techniques, particularly in the analysis of many thermally unstable compounds.
However, a thermally independent volatilization process, known as Rayleigh ion emission, provides a means to effect non-thermal volatilization of charged species from liquids. When the electric field at the surface of a droplet is of sufficient energy that the surface potential can be overcome, emission of charged species occurs from the droplet. This ion emission reduces the electrostatic repulsion experienced by an ion at the surface of the droplet. For ion emission to occur, the field at the surface of the droplet must exceed the Rayleigh instability number.
The conditions for Rayleigh instability are described in the following equation: EQU .alpha.=q.sup.2 /3U.tau..epsilon.
Instability occurs when .alpha.=4 where q is the charge on a drop, V is the volume, .tau. is the surface tension and .epsilon. is the dielectric constant. The critical radii for ion emission from water or other solvents or mixtures by Raleigh instability can, therefore, be calculated directly.
A droplet undergoing Rayleigh ion emission will lose a considerable fraction of the charge with only a small change in the radius. If the solvent is sufficiently volatile, evaporation will occur until the critical charge to radius ratio is exceeded, and Rayleigh emission will occur again. This happens because evaporation proceeds with virtually no loss of electrolyte. Aqueous electrolytic solvation energies are typically of the range 3-6 eV, and the probability of an ion escaping from the surface is calculated to be in the order of 10.sup.-50. If the droplet is in the micron size range, a competing process of ion evaporation can take place. In ion evaporation, ion clusters can be emitted from a charged droplet experiencing a large electric field applied at the surface. For these small droplets, the net charge on the droplet combined with its small radius is sufficient to produce an electric field at the surface of enough energy to allow ions to evaporate.
By passing gases through a very high potential electric field, non-thermal ionization can be accomplished by conduction and induction. If the field potential is greater than 10.sup.5 volts per meter, ionization of the gases and constituents of the gases occurs primarily by induction and independent of ion-molecule charge transfer reactions.
Ion emission by Rayleigh instability occurs in thermospray, atmospheric pressure ionization, ion evaporation and electrospray liquid chromatographic/mass spectrometric interfaces. However, all of these methods rely on the existence of preformed ions, or require additional electrolytes or buffers within the solvent from which a proton can be transferred to effect ionization of the analytes. Low dielectric, non-aqueous and aprotic solvents do not support ion formation, and as a result, few compounds exist in ionized form in these solvents. Thermospray, atmospheric pressure ionization, ion evaporation and electrospray are therefore primarily limited to aqueous solvent systems. Also, because of dependence on ion-molecule reactions to accomplish charge transfer, these methods, particularly atmospheric pressure ionization, ion evaporation and electrospray are limited to operational pressures near ambient. At reduced pressures, fewer ion-molecule collisions result in fewer charge transfer reactions. At increased pressures, evaporation of droplets is reduced. Droplet evaporation is necessary in these methods to accomplish ion emission by decreasing the droplet volume until the critical Rayleigh charge to radius limit is exceeded.
The use of an induction electrode in atmospheric pressure ionization and ion evaporation serves to increase the net charge on a droplet. In ion evaporation, the induction electrode is positioned adjacent to the liquid spray orifice. This type of system is disclosed in U.S. Pat. No. 4,300,044 to Iribarne et al. The charge on the electrode is opposite to the droplet charge at a potential of 1.5 to 3 kilovolts. This serves to increase the relative field strength experienced by ions at the surface of the droplet, to assist the ion emission process. The field generated is of insufficient strength to ionize either the solute or the solvent. Therefore, only polar solvents containing preformed ions can be used with this method.
The induction electrode in atmospheric pressure ionization liquid chromatography/mass spectrometry is positioned within the path of the sprayed droplets. This type of system is disclosed in U.S. Pat. No. 4,144,451 to Kambara. The electrode is of the same polarity as the ions to be analyzed, at an electric potential of typically 1.5 to 3.0 kilovolts. The electrode serves to increase the net charge on a droplet, primarily by conduction. However, the electromagnetic field generated by the induction electrode is of insufficient strength to ionize non-polar, organic and aprotic solvents or compounds. Water, or another polar or ionic compound is usually added to non-polar solvents to increase the relative amount of charge transfer in order to accomplish ionization. As such, non-polar solvents are observed as protonated molecular ions or ion clusters in positive ion mode.
In electrospray and related processes, electric potential is applied to the capillary which carries the liquid effluent. This type of system is disclosed in U.S. Pat. No. 4,209,696 to Fite. Charge transfer occurs by conduction through the solvent. High dielectric and non-polar solvents are not conductive by nature, and as a result, little charge is transfered to these solvent types. These solvents have not been used successfully with this method. The strength of an electromagnetic applied field is inversely proportional to the size of the field radiator. The field radiator in electrospray is the liquid chromatograph capillary, which is a large diameter conductor. Because of the large size of the field radiator, and the charge loss by conduction through the solvent, the liquid effluent at the droplet shearing point is subject to a reduced electric field. The field generated is of insufficient strength to ionize non-polar or aprotic solvents, even with applied voltages over 30 kilovolts.